Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pituitary
Published in: Pituitary 3/2013

01-09-2013

Pituitary disease mortality: is it fiction?

Authors: Eva Marie Erfurth, Peter Siesjö, Thomas Björk-Eriksson

Published in: Pituitary | Issue 3/2013

Login to get access

Abstract

During the last 20 years a tremendous improvement in the care of patients with pituitary tumors and of hypopituitarism has been achieved. If we resolve most of the possible causes of the increased cardiovascular disease and stroke mortality a normal survival is expected in these patients. Recently, a large population based study showed a decline in the risk of non-fatal stroke and of non-fatal cardiac events in GH deficient patients. This improvement was achieved by complete hormone replacement, including long term GH replacement, together with prescription of cardio protective drugs. If we follow the latest achievements in pituitary imaging, surgery techniques, hormone substitutions, cardio protective medications, we would expect a normal longevity in these patients. This review will focus on; (1) pituitary insufficiencies and hormone substitutions, (2) modes of cranial radiotherapy, and (3) new techniques in the surgery of a pituitary adenoma.
Literature
1.
Rosén T, Bengtsson BÅ (1990) Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285–288CrossRefPubMed
2.
Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM (1997) Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol 46:75–78CrossRef
3.
Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, Sheppard MC, Stewart PM West Midlands Prospective Hypopituitary Study Group (2001) Association between premature mortality and hypopituitarism. Lancet 357:425–431CrossRef
4.
Nielsen EH, Lindholm J, Laurberg P (2007) Excess mortality in women with pituitary disease: a meta-analysis. Clin Endocrinol (Oxf) 67(5):693–697CrossRef
5.
Stochholm K, Gravholt CH, Laursen T, Laurberg P, Andersen M, Kristensen LØ, Feldt-Rasmussen U, Christiansen JS, Frydenberg M, Green A (2007) Mortality and GH deficiency: a nationwide study. Eur J Endocrinol 157:9–18CrossRefPubMed
6.
Brada M, Ashley S, Ford D, Traish D, Burchell L, Rajan B (2002) Cerebrovascular mortality in patients with pituitary adenoma. Clin Endocrinol 57(6):713–717CrossRef
7.
Svensson J, Bengtsson BÅ, Rosén T, Odén A, Johannsson G (2004) Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab 89:3306–3312CrossRefPubMed
8.
Erfurth EM, Bulow B, Svahn-Tapper G, Norrving B, Odh K, Mikoczy Z, Bjork J, Hagmar L (2002) Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors. J Clin Endocrinol Metab 87:4892–4899CrossRefPubMed
9.
Barrett-Connor E (2003) Clinical review 162: cardiovascular endocrinology 3: an epidemiologist looks at hormones and heart disease in women. J Clin Endocrinol Metab 88:4031–4042CrossRefPubMed
10.
Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL (2004) Women’s health initiative steering committee. JAMA 291(14):1701–1712
11.
LaCroix AZ, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, Margolis KL, Stefanick ML, Brzyski R, Curb JD, Howard BV, Lewis CE, Wactawski-Wende J; WHI Investigators (2011) Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA 305(13):1305–1314
12.
Kannel WB (1989) Risk factors in hypertension. J Cardiovasc Pharmacol 13:4–10CrossRef
13.
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J (1990) Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335:765–777CrossRefPubMed
14.
Rosén T, Edén S, Larson G, Wilhelmsen L, Bengtsson BÅ (1993) Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh) 129:195–200
15.
Boger RH, Skamira C, Bode-Boger SM, Brabant G, von zur Muhlen A, Frolich JC (1996) Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest 98:2706–2713CrossRefPubMed
16.
Smith JC, Evans LM, Wilkinson I, Goodfellow J, Cockcroft JR, Scanlon MF, Davies JS (2002) Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study. Clin Endocrinol (Oxf) 56:493–501CrossRef
17.
Maison P, Griffin S, Nicoue-Beglah M, Haddad N, Balkau B, Chanson P, Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials (2004) Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials. J Clin Endocrinol Metab 89:2192–2199CrossRefPubMed
18.
Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN (1999) Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 84:453–457CrossRefPubMed
19.
Colao A, Di Somma C, Salerno M, Spinelli L, Orio F, Lombardi G (2002) The cardiovascular risk of GH-deficient adolescents. J Clin Endocrinol Metab 87:3650–3655CrossRefPubMed
20.
Borson-Chazot F, Serusclat A, Kalfallah Y, Ducottet X, Sassolas G, Bernard S, Labrousse F, Pastene J, Sassolas A, Roux Y, Berthezène F (1999) Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab 84:1329–1333CrossRefPubMed
21.
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine Society (2011) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(6):1587–1609CrossRefPubMed
22.
Abs R, Feldt-Rasmussen U, Mattsson AF, Monson JP, Bengtsson BA, Góth MI, Wilton P, Koltowska-Häggström M (2006) Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults—a KIMS database analysis. Eur J Endocrinol 5(1):79–90CrossRef
23.
Sesmilo G, Biller BM, Llevadot J, Hayden D, Hanson G, Rifai N, Klibanski A (2000) Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial. Ann Intern Med 133:111–122CrossRefPubMed
24.
Svensson J, Fowelin J, Landin K, Bengtsson B-Å, Johansson J-O (2002) Effects of seven years of growth hormone (GH) replacement therapy on insulin sensitivity in GH deficient adults. J Clin Endocrinol Metab 87:2121–2127CrossRefPubMed
25.
Bülow B, Erfurth EM (1999) A low individualized GH dose in young patients with childhood onset GH deficiency normalized serum IGF-I without significant deterioration in glucose tolerance. Clin Endocrinol (Oxf) 50(1):45–55
26.
Segerlantz M, Bramnert M, Manhem P, Laurila E, Groop LC (2003) Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults. Eur J Endocrinol 9(6):511–519CrossRef
27.
Follin C, Thilén U, Osterberg K, Björk J, Erfurth EM (2010) Cardiovascular risk, cardiac function, physical activity, and quality of life with and without long-term growth hormone therapy in adult survivors of childhood acute lymphoblastic leukemia. J Clin Endocrinol Metab 95(8):3726–3735CrossRefPubMed
28.
Holmer H, Svensson J, Rylander L, Johannsson G, Rosén T, Bengtsson BA, Thorén M, Höybye C, Degerblad M, Bramnert M, Hägg E, Edén Engström B, Ekman B, Norrving B, Hagmar L, Erfurth EM (2007) Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone. J Clin Endocrinol Metab 92(9):3560–3567CrossRefPubMed
29.
van Bunderen CC, van Nieuwpoort IC, Arwert LI, Heymans MW, Franken AA, Koppeschaar HP, van der Lely AJ, Drent ML (2011) Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch national registry of growth hormone treatment in adults. J Clin Endocrinol Metab 96(10):3151–3159
30.
Ho KK, Gibney J, Johannsson G, Wolthers T (2006) Regulating of growth hormone sensitivity by sex steroids: implications for therapy. Front Horm Res 35:115–128CrossRefPubMed
31.
Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA (1997) Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 82:550–555CrossRefPubMed
32.
Gibney J, Wolthers T, Johannsson G, Umpleby AM, Ho KK (2005) Growth hormone and testosterone interact positively to enhance protein and energy metabolism in hypopituitary men. Am J Physiol Endocrinol Metab 289(2):E266–E271CrossRefPubMed
33.
Grunfeld C, Sherman B, Cavalieri R (1988) The acute effects of human growth hormone administration on thyroid function in normal men. J Clin Endocrionol Metab 67:1111–1114CrossRef
34.
Porretti S, Giavoli C, Ronchi C, Lombardi G, Zaccaria M, Valle D, Arosio M, Beck-Peccoz P (2002) Recombinant human GH replacement therapy and thyroid function in a large group of adult GH-deficient patients: when does L-T(4) therapy become mandatory? J Clin Endocrinol Metab 87(5):2042–2045CrossRefPubMed
35.
Jörgensen J, Pedersen A, Laurberg P (1989) Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central Hypothyroidism. J Clin Endocrinol Metab 69:1127–1132CrossRefPubMed
36.
Agha A, Monson JP (2007) Modulation of glucocorticoid metabolism by the growth hormone—IGF-1 axis. Clin Endocrinol (Oxf) 66(4):459–465
37.
Howlett TA (1997) An assessment of optimal hydrocortisone replacement therapy 46(3):263–268
38.
Filipsson H, Monson JP, Koltowska-Häggström M, Mattsson A, Johannsson G (2006) The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. J Clin Endocrinol Metab 91:3954–3961CrossRefPubMed
39.
Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engström BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Biller BM, Monson JP, Stewart PM, Lennernäs H, Skrtic S (2012) Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab 97(2):473–481CrossRefPubMed
40.
Buchfelder M, Schlaffer S (2009) Surgical treatment of pituitary tumors. Best Pract Res Clin Endocrinol Metabol 23:677–692CrossRef
41.
DeKlotz TR, Chia SH, Lu W, Makambi KH, Aulisi E, Deeb Z (2012) Meta-analysis of endoscopic versus sublabial pituitary surgery. Laryngoscope 122(3):511–518CrossRefPubMed
42.
Strychowsky J, Nayan S, Reddy K, Farrokhyar F, Sommer D (2011) Purely endoscopic transsphenoidal surgery versus traditional microsurgery for resection of pituitary adenomas: systematic review. J Otolaryngol Head Neck Surg 40:175–185PubMed
43.
Buchfelder M, Kreutzer J (2008) Transcranial surgery for pituitary adenomas. Pituitary 11:375–384CrossRefPubMed
44.
Barzaghi LR, Losa M, Giovanelli M, Mortini P (2007) Complications of transsphenoidal surgery in patients with pituitary adenoma: experience at a single centre. Acta neurochirurgica 149:877–885, discussion 885–876
45.
Müslüman AM, Cansever T, Yılmaz A, Kanat A, Oba E, Çavuşoğlu H, Sirinoğlu D, Aydın Y. (2011) Surgical results of large and giant pituitary adenomas with special consideration of ophthalmologic outcomes. WNEU 76:141–148, discussion 163–146
46.
Nomikos P, Buchfelder M, Fahlbusch R (2005) The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical cure. Eur J Endocrinol 152:379–387CrossRefPubMed
47.
Kurwale NS, Ahmad F, Suri A, Kale SS, Sharma BS, Mahapatra AK, Suri V, Sharma MC (2012) Post operative pituitary apoplexy: preoperative considerations toward preventing nightmare. Br J Neurosurg 26:59–63CrossRefPubMed
48.
Sinha S, Sharma BS (2010) Giant pituitary adenomas–an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients. Br J Neurosurg 24:31–39CrossRefPubMed
49.
Tabaee A, Anand VK, Barrón Y, Hiltzik DH, Brown SM, Kacker A, Mazumdar M, Schwartz TH (2009) Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg 111:545–554CrossRefPubMed
50.
Patil CG, Lad SP, Harsh GR, Laws E R, Boakye M (2007) National trends, complications, and outcomes following transsphenoidal surgery for Cushing’s disease from 1993 to 2002. Neurosurg Focus 23:1–6
51.
Puri AS, Zada G, Zarzour H, Laws E, Frerichs K (2012) Cerebral vasospasm after transsphenoidal resection of pituitary macroadenomas: report of 3 cases and review of the literature. Neurosurgery 71:173–181CrossRefPubMed
52.
Raymond J, Hardy J, Czepko R, Roy D (1997) Arterial injuries in transsphenoidal surgery for pituitary adenoma; the role of angiography and endovascular treatment. AJNR 18:655–665PubMed
53.
Ciric I, Ragin A, Baumgartner C, Pierce D (1997) Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 40:225–236, discussion 236–227
54.
Erturk E, Tuncel E, Kiyici S, Ersoy C, Duran C, Imamoglu S (2005) Outcome of surgery for acromegaly performed by different surgeons: importance of surgical experience. Pituitary 8:93–97CrossRefPubMed
55.
Sutton LN, Gusnard D, Bruce DA, Fried A, Packer RJ, Zimmerman RA (1991) Fusiform dilatations of the carotid artery following radical surgery of childhood craniopharyngiomas. J Neurosurg 74:695–700CrossRefPubMed
56.
Sughrue ME, Chang EF, Gabriel RA, Aghi MK, Blevins LS (2011) Excess mortality for patients with residual disease following resection of pituitary adenomas. Pituitary 14:276–283CrossRefPubMed
57.
58.
O’Connor MM, Mayberg MR (2000) Effects of radiation on cerebral vasculature: a review. Neurosurgery 46:138–151CrossRefPubMed
59.
Hopewell JW, Campling D, Calvo W, Reinhold HS, Wilkinson JH, Yeung TK (1986) Vascular irradiation damage: its cellular basis and likely consequences. Br J Cancer 7:181–191
60.
Ronson BB, Schulte RW, Han KP, Loredo LN, Slater JM, Slater JD (2006) Fractionated proton beam irradiation of pituitary adenomas. Int J Radiat Oncol Biol Phys 64:425–434CrossRefPubMed
61.
Becker G, Kocher M, Kortmann RD, Paulsen F, Jeremic B, Müller RP, Bamberg M (2002) Radiation therapy in the multimodal treatment approach of pituitary adenoma. Strahlenther Onkol 178(4):173–186CrossRefPubMed
62.
Mackley HB, Reddy CA, Lee SY, Harnisch GA, Mayberg MR, Hamrahian AH, Suh JH (2007) Intensity-modulated radiotherapy for pituitary adenomas: the preliminary report of the Cleveland clinic experience. Int J Radiat Oncol Biol Phys 67:232–239CrossRefPubMed
63.
Leksell DG (1987) Stereotactic radiosurgery. Present status and future trends. Neurol Res 9(2):60–68PubMed
64.
Milker-Zabel S, Debus J, Thilmann C, Schlegel W, Wannenmacher M (2001) Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland. Int J Radiat Oncol Biol Phys 50(5):1279–1286CrossRefPubMed
65.
Minniti G, Jaffrain-Rea ML, Osti M, Cantore G, Enrici RM (2007) Radiotherapy for nonfunctioning pituitary adenomas: from conventional to modern stereotactic radiation techniques. Neurosurg Rev 30(3):167–175CrossRefPubMed
66.
Littley M, Shalet S, Reid H (1991) The effect of external pituitary irradiation on elevated serum prolactin levels in patients with pituitary macroadenomas. Q J Med 81:985–998CrossRefPubMed
67.
Vladyka V, Liscak R, Novotny J, Marek J, Jezkova J (2003) Radiation tolerance of functioning pituitary tissue in gamma knife surgery for pituitary adenomas. Neurosurgery 52:309–317CrossRefPubMed
68.
Minniti G, Gilbert DC, Brada M (2009) Modern techniques for pituitary radiotherapy. Rev Endocr Metab Disord 10:135–144CrossRefPubMed
69.
Sattler MG, van Beek AP, Wolffenbuttel BH, van den Berg G, Sluiter WJ, Langendijk JA, van den Bergh AC (2012) The incidence of second tumors and mortality in pituitary adenoma patients treated with postoperative radiotherapy versus surgery alone. Radiother Oncol 104(1):125–130CrossRefPubMed
70.
Brummelman P, Elderson MF, Dullaart RP, van den Bergh AC, Timmer CA, van den Berg G, Koerts J, Tucha O, Wolffenbuttel BH, van Beek AP (2011) Cognitive functioning in patients treated for nonfunctioning pituitary macroadenoma and the effects of pituitary radiotherapy. Clin Endocrinol 74(4):481–487CrossRef
71.
Brummelman P, Sattler MG, Meiners LC, Elderson MF, Dullaart RP, van den Berg G, Koerts J, Tucha O, Wolffenbuttel BH, van den Bergh AC, van Beek AP (2012) Cognitive performance after postoperative pituitary radiotherapy: a dosimetric study of the hippocampus and the prefrontal cortex. Eur J Endocrinol 166(2):171–179CrossRefPubMed
72.
Ayuk J (2012) Does pituitary radiotherapy increase the risk of stroke and, if so, what preventative actions should be taken? Clin Endocrinol 76(3):328–331CrossRef
73.
Sherlock M, Reulen RC, Alonso AA, Ayuk J, Clayton RN, Sheppard MC, Hawkins MM, Bates AS, Stewart PM (2009) ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly. J Clin Endocrinol Metab 94(11):4216–4223CrossRefPubMed
Metadata
Title
Pituitary disease mortality: is it fiction?
Authors
Eva Marie Erfurth
Peter Siesjö
Thomas Björk-Eriksson
Publication date
01-09-2013
Publisher
Springer US
Published in
Pituitary / Issue 3/2013
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-013-0469-1

Other articles of this Issue 3/2013

Pituitary 3/2013 Go to the issue

OriginalPaper

Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing’s syndrome

OriginalPaper

Severe growth hormone deficiency is rare in surgically-cured acromegalics

OriginalPaper

Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence

OriginalPaper

The impact of sleep apnea treatment on carbohydrate metabolism in patients with acromegaly

OriginalPaper

A consensus on the diagnosis and treatment of acromegaly complications

ReviewPaper

Pituitary stem cells: candidates and implications
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits